1. Field
The present disclosure relates to compositions for reducing cell senescence, methods of reducing cell senescence in mammals, and methods of treating cell senescence-related symptoms in mammals.
2. Description of the Related Art
Senescence may be defined as a permanent halt of cellular division. Replicative senescence or cellular senescence has been observed as an aging model at the cellular level. When cells are continuously cultured, cells divide a number of times, but aged cells can no longer divide. Senescent cells are resistant against programmed cell death, and some senescent cells are maintained in a non-dividing state for several years.
Rho-kinase is a kinase that belongs to the AGC (PKA/PKG/PKC) family of serine-threonine kinases. Rho-associated protein kinases (i.e., ROCKs) including ROCK1 and ROCK2, are found in mammals, zebrafish, Xenopus, and the like. Human ROCK1 has a molecular mass of 150 kDa and is a major downstream effector of small GTPase RhoA. Mammal ROCK includes a kinase domain, a coiled-coil region, and a Pleckstrin homology (PH) domain, which reduces the kinase activity of ROCKs by autoinhibitory intramolecular fold if RhoA-GTP is not present.
Because of the role that ROCKs play in cellular processes associated with cellular senescence, there remains a need to develop compositions and methods of reducing cell senescence with Rho-kinase inhibitors.